Expression and release of LAG‐3‐encoded protein by human CD4 ⁺ T cells are associated with IFN‐γ production

The lymphocyte activation gene (LAG) ‐3 is a member of the immunoglobulin superfamily that is selectively transcribed in human activated T and NK cells. In this work, the possibility that LAG‐3 expression by human CD4 + T cells was preferentially related to one or another phenotype of cytokine secretion was investigated. Surface LAG‐3 expression correlated with IFN‐γ, but not IL‐4, production in antigen‐stimulated T cells and it was up‐ regulated by IL‐12. Most activated CD4 + T cell clones with established Thl or Th0 profiles of cytokine secretion expressed LAG‐3 on their surface, whereas the great majority of Th2 clones showed 1 neither surface LAG‐3 nor LAG‐3 mRNA expression. After activation, the majority of CD4 + T cell clones also released soluble LAG‐3‐related peptides, and such a release correlated positively with the production of IFN‐γ and inversely with the production of IL‐4. Thus, LAG‐3 expression by activated CD4 + human T cells appear to be preferentially associated with the differentiation/activation pathway leading to the production of IFN‐γ.—Annunziato, F., Manetti R., Tomase vie, L., Guidizi, M.‐G., Biagiotti, R., Giannö, V., Germano, P., Mavilia, C., Maggi, E., Romagnani, S. Expression and release of LAG‐3‐encoded protein by human CD4 + T cells are associated with IFN‐γ production. FASEB J. 10, 769‐775 (1996)